In a themed issue on HIV – appearing just before the International AIDS Conference in Durban, South Africa, begins this weekend -- the recommendations also endorse the use of pre-exposure prophylaxis with antiretroviral therapy for at-risk individuals, reported Huldrych Gunthard, MD, of University Hospital Zurich in Switzerland, and colleagues.

"There have been substantial advances in the use of antiretroviral drugs for the treatment and prevention of HIV infection since the last version of these recommendations in 2014, warranting an update to the recommendations," Gunthard and colleagues wrote. "With rare exception, all HIV-infected individuals with detectable viremia, regardless of their CD4 cell count, should begin antiretroviraltherapy as soon as possible after diagnosis to prevent disease progression, improve clinical outcomes and limit transmission. This recommendation is strongly supported by recent large randomized clinical trials."

The authors also asserted that "new drugs that combine excellent potency with greater convenience, safety, and tolerability make lifelong viral suppression achievable and reduce the risk of viral resistance. In HIV-infected persons, antiretroviral therapy is effective in preventing HIV transmission and provides individual and public health benefits. When used effectively, currently available antiretrovirals can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults."

In addition, Gunthard and colleagues recommended the use of antiretroviral therapy for individuals at risk of acquiring HIV infection -- either for postexposure prophylaxis or pre-exposure prophylaxis to prevent HIV acquisition.

The new guidelines suggest that the initial treatment for individuals diagnosed with HIV infection should be the combination of two nucleoside/nucleotide reverse transcriptase inhibitors with an integrase strand transfer inhibitor. The recommendations also suggest that "other effective regimens include non-nucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two nucleoside reverse transcriptase inhibitors."

Gunthard and colleagues noted that the recommendations are the work of an international panel of 14 volunteer experts in HIV research and patient care appointed by the International Antiviral Society–USA. Potential members were screened for expertise in the field, involvement in research and care, financial relationships with commercial companies, and ability to work toward consensus.

"These recommendations are focused on adults with or at risk of HIV infection in settings in which most antiretrovirals are available or in late-stage development," the researchers suggested.

In an editorial that accompanies the guidelines, Kenneth Mayer, MD, and Douglas Krakower, MD, of Beth Israel Deaconess Medical Center/Harvard University, wrote, "The current IAS-USA guidelines reflect the hard-won success of 35 years of clinical research.

"Although challenges remain to optimize the cascade of care and to prevent new infections, and an aging epidemic will present new challenges, these concerns reflect the successes of highly effective antiretroviral therapy," they wrote. "Historians may wonder whether the pace of discovery in the early days of the epidemic could have been accelerated, but no one can doubt the signal accomplishments of biobehavioral research and community engagement in forging a common strategy to deal with this global pandemic, one that continues to pose new challenges."

The recommendations particularly elevate integrase inhibitor based regimens to what the Gunthard and colleagues termed the "optimal treatment" for initial HIV therapy, mainly because that the use of integrase inhibitors appears to offer a greater barrier to the development of resistant. The recommendations include the use of combination and co-formulations of the integrase inhibitors dolutegravir (Tivicay), elvitegravir (Viteka), and raltegravir (Isentress). The guidelines suggest the use of tenofovir alafenamide as one of the nucleoside reverse transcriptase inhibitors, but say that tenofovir disoproxil fumarate may also be appropriate if the newer tenofovir formulation is not available.

In their commentary, Mayer and Krakower noted that integrase inhibitors have been cited as the cornerstone of treatment for multiple reasons. "... these drugs have been shown to be highly effective, with the highest and most rapid rates of virologic suppression compared with protease inhibitors and non-nucleoside reverse transcriptase inhibitors, which previously had been mainstays of the antiretroviral 'cocktail.' Moreover, integrase strand transfer inhibitors are extremely well tolerated and several are co-formulated with nucleoside analogs, allowing for potent, well-tolerated treatment to be delivered as a single pill taken once a day."

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